When taken as prescribed, antiretroviral therapy (ART) has dramatic effects on the health and well-being of HIV+ individuals. HIV+ persons on ART, however, must adhere rigorously to an often complex and side-effect prone therapeutic regimen to benefit from this therapy, and to avoid contracting treatment resistant strains of HIV that can potentially be transmitted to others. While 95% adherence to ART is critical for viral suppression, actual adherence rates of 60-70% and lower are common in HIV+ clinical samples. Although suboptimal adherence to ART may have extremely serious individual and public health consequences, few theory-based, rigorously evaluated interventions to increase adherence to ART have been implemented and found to be effective in clinical care settings. Most extant approaches to enhancing adherence to ART involve labor-intensive, individually focused interventions, which have yet to demonstrate efficacy, and which are too intensive and too expensive to deploy widely. Overall, the standard-of-care for ART adherence in HIV clinical settings is ad hoc and minimal. This proposal involves the development, piloting, implementation, and rigorous evaluation of an innovative approach to assisting HIV+ individuals to adhere to ART. It uses the Information - Motivation - Behavioral Skills (IMB) model of adherence (J. Fisher, 2000a; J. Fisher et al., 2002a; W. Fisher et al., in press) to design, implement and evaluate an individualized, interactive, cost-effective, computer-assisted ART adherence intervention that can be widely implemented in clinical care settings. The intervention will use Motivational Interviewing techniques (e.g., Rollnick et al., 2000) as a delivery system for conveying individually tailored ART adherence-related information, motivation, and behavioral skills (IMB) content to HIV+ patients about to begin ART, to facilitate high levels of initial adherence, and to patients on ART, to enhance adherence and promote maintenance of optimal levels of adherence. The ART adherence intervention will be compared with an appropriate standard-of-care control group in terms of mutiple indicators of ART adherence in evaluation outcome research over an 18-month follow-up interval. The standard-of-care control group will also permit us to study the natural history of ART adherence and its longitudinal dynamics, as a function of factors such as changes in subjective and objective health, substance abuse status, disease stage, length of time on ART, and other factors. This, in its own right, also represents an important contribution to ART adherence research.